Role of p53 and apoptosis in sensitization of cis-diamminedichloroplatinum antitumor activity by interleukin-1 in ovarian carcinoma cells.
We have previously reported that interleukin-1 (IL-1 ) sensitized cisplatin cytotoxicity against human ovarian NIH:OVCAR-3 tumor cells. We have further examined inter-actions of IL-1 with cisplatin in these ovarian cells. Treatment of cells with either IL-1 or CDDP or combinations resulted in a significant accumulation of cells in G1 phase and a concomitant decrease in the S phase of the cell cycle. IL-1 and CDDP treatment induced p53 protein in NIH:OVCAR-3 tumor cells. CDDP and IL-1 treatment decreased the steady-state expression of c-myc RNA and induced significant degradation of the genomic DNA into internucleosomal sized DNA fragments which was further increased in the presence of both agents in these cells. Taken together, these studies suggest that IL-1 may kill ovarian NIH:OVCAR-3 tumor cells by inducing a blockade at G1/S of the cell cycle, down-regulating c-myc gene and inducing p53-dependent apoptosis. The synergistic interactions of IL-1 with CDDP may involve the enhancement of p53-dependent apoptosis.
Song
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K
Developmental Therapeutics Department, Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Fukushima
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P
Seth
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Sinha
B K
BK
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D053938:DNA Fragmentation / Q000235:genetics; D015536:Down-Regulation; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology* / Q000627:therapeutic use; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects* / Q000378:metabolism
D007375:Interleukin-1; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin